Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
ISOLATION OF PARTIALLY PURIFIED P450 2D18 AND CHARACTERIZATION OF ACTIVITY TOWARD THE TRICYCLIC ANTIDEPRESSANTS IMIPRAMINE AND DESIPRAMINE
Autore:
THOMPSON CM; KAWASHIMA H; STROBEL HW;
Indirizzi:
UNIV TEXAS,SCH MED,DEPT BIOCHEM & MOL BIOL,POB 20708 HOUSTON TX 77225 OSAKA CITY UNIV,SCH MED,DEPT UROL OSAKA 5458586 JAPAN
Titolo Testata:
Archives of biochemistry and biophysics (Print)
fascicolo: 1, volume: 359, anno: 1998,
pagine: 115 - 121
SICI:
0003-9861(1998)359:1<115:IOPPP2>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT-BRAIN CYTOCHROME-P450; CDNA-DIRECTED EXPRESSION; FUNCTION OXIDASE SYSTEM; IN-VITRO METABOLISM; C6 CELL-LINE; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; PROTEIN EXPRESSION; ESCHERICHIA-COLI; HIGH-LEVEL;
Keywords:
CYTOCHROME P450; CYP2D18; CYP2D6; CYP2D4; PROTEIN EXPRESSION; BACULOVIRUS; ENZYME PURIFICATION; IMIPRAMINE; DESIPRAMINE; TRICYCLIC ANTIDEPRESSANTS; GBR-12935; BRAIN DRUG METABOLISM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
43
Recensione:
Indirizzi per estratti:
Citazione:
C.M. Thompson et al., "ISOLATION OF PARTIALLY PURIFIED P450 2D18 AND CHARACTERIZATION OF ACTIVITY TOWARD THE TRICYCLIC ANTIDEPRESSANTS IMIPRAMINE AND DESIPRAMINE", Archives of biochemistry and biophysics (Print), 359(1), 1998, pp. 115-121

Abstract

Previous reports have shown that rat brain microsomes are capable of metabolizing tricyclic antidepressants such as imipramine, Subsequent studies have shown that the protein products of several clones isolated from rat brain cDNA libraries are capable of metabolizing imipramineto both its active metabolite, desipramine, and its inactive hydroxylated metabolites. We report here the overexpression and partial purification of P450 2D18 using the baculovirus expression system and the incorporation of a C-terminal [His](4) tag,P450 2D18 was partially purified to a specific content of 4.8 nmol/mg protein and shown to be electrophoretically pure. The apparent K-M values for P450 2D18 toward imipramine and desipramine were 374 and 314 mu M, respectively. While apparent K-M values were similar, P450 2D18 was shown to have a five-fold increased V-max (2.2 nmol/min/nmol P450) for imipramine compared to desipramine (0.44 nmol/min/nmol P450), suggesting a primary involvement in the activation of imipramine to desipramine. We also examined the effect of the CYP2D6 inhibitor quinidine, the CYP3A inhibitor ketoconazole, and the dopamine reuptake inhibitor GBR-12935 for their ability to inhibit P450 2D18-mediated metabolism of imipramine. These results, when compared with previous studies using rat brain microsomes, suggest that P450 2D18 may play an important role in the conversion of imipramine to its active metabolite desipramine in the rat brain. (C) 1998 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 02:53:07